New Cholesterol Drugs Face Setbacks

NEW ORLEANS – The hot new strategy of trying to prevent heart disease by raising good cholesterol had more setbacks Monday as new studies showed that experimental drugs didn't work and also had safety problems.

The news follows Pfizer Inc.'s abandonment in December of an $800 million investment in torcetrapib, the leading contender in this class of drugs, because it raised the risk of heart attacks and deaths.

Heart specialists have been anxious to know whether the problems extend to all such drugs and doom this approach.

"A lot of people think it's the next big thing, and we'll need to understand what went wrong with torcetrapib to move forward," said Dr. Steven Nissen, a Cleveland Clinic heart specialist who is president of the American College of Cardiology.

The new studies, reported at the group's conference, gave a mixed answer. The Pfizer drug seems uniquely risky, but other drugs have problems, too.

And even though they and the Pfizer drug raised HDL good cholesterol as intended, that made no difference in the odds of heart attacks or deaths, or key measures of cholesterol buildup in arteries.

Doctors long have focused on lowering LDL, or bad cholesterol, to cut heart attack risk. Statins, sold as Lipitor and Zocor and also in generic form, lower LDL, which ferries fats from food into the bloodstream.

But many statin users suffer heart attacks anyway, so doctors have been trying to boost HDL, or good cholesterol -- which transports fat from the blood to the liver to be disposed of -- to further lower risk.

An extended-release niacin drug called Niaspan, sold by Kos Pharmaceuticals Inc., does this. But it can cause a prickly hot sensation called flushing that some people find intolerable. Pfizer, Merck & Co. and Swiss drug maker Roche Holding AG are testing drugs that boost HDL in a novel way.

On Monday, scientists reported the results of several studies on torcetrapib. In one, the drug boosted HDL by 61 percent, but trends in death, hospitalization and heart attacks "are all going in the wrong direction," Nissen said.

An experimental diabetes drug by Eli Lilly and Co. that is 10,000 times more potent than fibrates, a current cholesterol treatment, also proved disappointing. The new drug raised HDL but also raised the risk of kidney, heart and other serious problems, Nissen reported.

Finally, infusions of a reconstituted form of HDL developed by CSL Ltd., an Australian company, made no big difference in the burden of artery buildups in a study led by Dr. Jean-Claude Tardif of the Montreal Heart Institute.

In several of these studies there were hints of some improvements in less important measures of artery buildup, which provides "a glimmer of hope for future development of this class of drugs," Dr. Alan Tall of Columbia University writes in an editorial in the New England Journal of Medicine.

That journal and the Journal of the American Medical Association published several of the new studies.

"The bar has been raised a lot for this entire class, but I do not think we can abandon this entire approach," Nissen said.

If Baycol had been the first statin tested and research had stopped after safety problems emerged, there wouldn't even be this class of drugs, he noted. Baycol, sold by Bayer AG, was withdrawn from the market in 2001 after reports of a severe and sometimes fatal muscle disorder.